Composition Comprising Lactobacillus Plantarum 2830 (ECGC 13110402)

ABSTRACT

The present invention relates to compositions comprising  Lactobacillus plantarum  2830 (ECGC 13110402), or mutant strain or strains thereof, for use in the treatment or prevention of hypertension.

TECHNICAL FIELD OF THE INVENTION

The invention relates to a composition comprising Lactobacillusplantarum 2830 (ECGC 13110402) which has been shown to be useful in thetreatment, prevention and/or management of hypertension.

BACKGROUND TO THE INVENTION

Hypertension, otherwise known as high blood pressure, is a major healthproblem and is a risk factor for cardiovascular disease (CVD). The WorldHealth Organisation (WHO) predicts that by the year 2020, up to 40% ofall human deaths will be related to CVD. High cholesterol is oftenlinked to hypertension due to a build up of cholesterol plaque in bloodvessels.

Treatments for hypertension include angiotensin-converting enzyme (ACE)inhibitors, calcium channel blockers, diuretics and beta-blockers.However, all of these treatments are not without their side effects andtherefore alternative or more natural treatments would be preferable.

The use of microbial strains in the reduction of cholesterol levels, andtherefore potentially hypertension, by regulating bile acid regulatorsis known. Bile Salt Hydrolase (BSH) active probiotics have been shown toincrease intraluminal bile acid deconjugation, resulting in increasedlevels of circulating deconjugated bile salts in humans and animalstudies. As bile acids are deconjugated in the intestines, dietary andbiliary cholesterol absorption is reduced and the recirculation of bileis altered, resulting in better control of low density lipoproteincholesterol (LDL-C) levels in blood.

Studies have suggested a role of probiotics in reducing blood pressure.A meta-analysis of nine trials (Khalesi et. al., (2014), Hypertension,64, (4), 897-903) showed probiotic consumption changed systolic BP by−3.56 mm Hg (95% confidence interval, −6.46 to −0.66) and diastolic BPby −2.38 mm Hg (95% confidence interval, −2.38 to −0.93) compared withcontrol groups.

It is therefore an object of the present invention to provide animproved or alternative treatment for hypertension. It is also an objectto provide a method of controlling or reducing blood pressure in anindividual, and in particular, those having mild hypercholesterolaemia.It is a further object of the present invention to provide a probioticcomposition which can be employed to reduce hypertension.

SUMMARY OF THE INVENTION

In an aspect of the present invention, there is provided a compositioncomprising Lactobacillus plantarum 2830 (ECGC 13110402), or mutantstrain or strains thereof, for use in the treatment, control orprevention of hypertension.

In another aspect of the present invention, there is provided acomposition comprising Lactobacillus plantarum 2830 (ECGC 13110402), ormutant strain or strains thereof, for use in the treatment, control orprevention of hypertension.

In a further aspect of the present invention, there is provided acomposition comprising Lactobacillus plantarum 2830 (ECGC 13110402), ormutant strain or strains thereof, for use in the manufacture of amedicament for the treatment, control or prevention of hypertension.

It is preferred that the use of the composition in the treatment orprevention of hypertension is in an individual having at least mildhypercholesterolaemia.

In a yet further aspect of the present invention, there is provided afoodstuff or food supplement composition comprising Lactobacillusplantarum 2830 (ECGC 13110402), or mutant strain or strains thereof, foruse in the reduction, prevention and/or control or hypertension.

In a yet further aspect of the present invention, there is provided acomposition comprising Lactobacillus plantarum 2830 (ECGC 13110402), ormutant strain or strains thereof, for use in the manufacture of a foodsupplement or foodstuff for the treatment, control or prevention ofhypertension.

In all aspects, the Lactobacillus plantarum 2830 (ECGC 13110402), ormutant strain or strains thereof, will preferably be present in thecomposition in an effective amount so as to reduce, prevent or controlhypertension. Preferably, the Lactobacillus plantarum will beadministered to an individual in an amount in the range of 10⁵ cfu/g to10¹² cfu/g. More preferably, will be administered in an amount in therange of 10⁸ cfu/g to 10¹⁰ cfu/g. The Lactobacillus plantarum may beadministered to an individual in an amount in the range of 1×10⁵ cfu to1×10¹² cfu. More preferably, will be administered in an amount in therange of 1×10⁸ cfu to 1×10¹⁰ cfu. Most preferably, the Lactobacillusplantarum is in an amount of about 120 mg of the active strain providingabout 1.8×10⁹ cfu. Although it will be appreciated that differentdosages may be administered depending upon the individuals' conditionand degree of hypertension and other medical considerations.

Administration frequency would also be dependent upon an individuals'condition but preferably the composition would be administered twicedaily.

The composition may be administered at any time of day, but preferablythe composition is adminstered after meals. Administration after a mealadvantageously accentuates the deconjugation effect of the BSH activeLactobacillus plantarum. Most bile acid secretion occurs after theconsumption of a meal and the amount of bile acid secreted isproportionally related to the amount and type of food consumed.

It will be apparent to the skilled addressee that the composition may bein any easily administered form, for example in the form of a powder,tablet, or capsule. Alternatively, the composition may be in the form ofa food stuff or food additive. The composition may be in the form of adrinkable liquid, a spread and/or powder which can be mixed with a solidor liquid food stuff. The composition could be used as a dietarysupplement—for example to be blended with foods/drinks or consumedalongside foods/drinks.

The composition may further comprise an excipient or carrier compound tomodify the release profile of one or more of the components through theintestinal environment. Release should occur at the most appropriatetime in for reducing cholesterol absorption and thus controlhypertension. Typically, the culture must survive relatively intactuntil it reaches the intestinal enterocytes of the small intestine.

The composition may be encapsulated. Many encapsulation techniques willbe apparent to the skilled addressee and the one employed will betailored to the required stability of the Lactobacillus plantarum duringdigestive transit. The encapsulate may comprise a prebiotic specificallytailored to the Lactobacillus plantarum.

The Lactobacillus plantarum may be concentrated and/or freeze dried.Advantageously Lactobacillus plantarum 2830 (ECGC 13110402) hasdemonstrated excellent freeze drying survival in pilot scalemanufacturing trials.

The composition may further comprise one or more active ingredientsselected from: vitamins, minerals, phytochemicals, antioxidants, andcombinations thereof.

Vitamins may include fat soluble vitamins such as vitamin A, vitamin D,vitamin E, and vitamin and combinations thereof. In some embodiments,vitamins can include water soluble vitamins such as vitamin C (ascorbicacid), the B vitamins (thiamine or B 1, riboflavoin or B25 niacin or B3,pyridoxine or B6, folic acid or B9, cyanocobalimin or B12, pantothenicacid, biotin), and combinations thereof.

Minerals may include, but are not limited to, sodium, magnesium,chromium, iodine, iron, manganese, calcium, copper, fluoride, potassium,phosphorous, molybdenum, selenium, zinc, and combinations thereof.

Antioxidants may include but are not limited to ascorbic acid, citricacid, rosemary oil, vitamin A, vitamin E, vitamin E phosphate,tocopherols, di-alpha-tocopheryl phosphate, tocotrienols, alpha lipoicacid, dihydrolipoic acid, xanthophylls, beta cryptoxanthin, lycopene,lutein, zeaxanthin, astaxanthin, beta-carotene, carotenes, mixedcarotenoids, polyphenols, fiavonoids, and combinations thereof.

Phytochemicals may include but are not limited to cartotenoids,chlorophyll, chlorophyllin, fiber, flavanoids, anthocyamns, cyaniding,delphinidin, malvidin, pelargonidin, peonidin, petunidin, flavanols,catechin, epicatechin, epigallocatechin, epigailocatechingallate,theaflavins, thearubigins, proanthocyanins, flavonols, quercetin,kaempferol, myricetin, isorhamnetin, flavononeshesperetin, naringenin,eriodictyol, tangeretin, flavones, apigenin, luteolin, lignans,phytoestrogens, resveratrol, isoflavones, daidzein, genistein,glycitein, soy isoflavones, and combinations thereof.

The composition may further comprise one or more cholesterol reducingagents. For instance the composition may comprise beta glucans.

The composition may be administered with one or more statins, sterolsand/or stanols. The composition may be co-administration with otherhypertension active increments or used in as part of a combinationtherapy with such active ingredients to reduce the quantity ofingredients administered and therefore limit side effects.

Preferably the composition is stored at 4° C. or below. Bacterial growthis stabilised in this temperature range thus ensuring the stability ofthe composition.

The composition may further comprise a prebiotic growth medium which isspecific to the growth of the Lactobacillus plantarum strain. Theprebiotic growth medium will preferably be capable of being producing bythe Lactobacillus plantarum strain by reverse enzyme reaction. Theenzyme may comprise a saccharolytic or glycosidase enzymes. Thesesaccharolytic or glycosidase enzymes may be derived from bacteria orfungi.

The prebiotic growth medium may comprise oligosaccharides such asgalacto-oligosacharides, (GOS), gluco-oligosacharides, orfructo-oligosaccharides (FOS) in varying concentrations. It is preferredthat the oligosaccharide form is substantially the same as the formproduced by β-galactosidases, α-galactosidases, α- and β-glucosidases,α-mannosidases and β-xylosidases reverse reactions of the strain.

The prebiotic growth medium may be present in an amount which providesoptimal growth and survival of the strain within the gut withoutimpacting on safety, tolerance, and shelf life.

In accordance with a further aspect of the present invention, there isprovided a method of treating an individual with or at risk of elevatedhypertension by administering a composition having an effective amountof the Lactobacillus plantarum.

In accordance with a further aspect of the present invention, there isprovided Lactobacillus plantarum 2830 (ECGC 13110402), or mutant strainor strains thereof, for use in a method of preventing, treating ormodulating hypertension, wherein the Lactobacillus plantarum isadministered in an amount in the range of 1×10⁵ to 10¹² cells twice aday.

More preferably, the Lactobacillus plantarum may be administered in anamount in the range of 1×10⁸ to 1×10¹⁰ cells. Most preferably, theLactobacillus plantarum is administered in an amount about 1.8×10⁹cells. Also preferably, the Lactobacillus plantarum is administered inan amount of about 120 mg of the active strains.

The Lactobacillus plantarum may be administered shortly before, duringor after morning and evening meals. Preferably, the Lactobacillusplantarum is administered shortly before breakfast and the evening meal.

The Lactobacillus plantarum may be administered as a medicine or as adietary supplement.

The Lactobacillus plantarum may be in a freeze dried form.

The Lactobacillus plantarum may be administered with one or moreadditional hypertension active ingredient components. Such componentsmay comprises: angiotensin-converting enzyme (ACE) inhibitors, calciumchannel blockers, diuretics or beta-blockers. Furthermore, theLactobacillus plantarum may be administered with one or more probioticsand/or prebiotics. The Lactobacillus plantarum may be administered incombination with a prebiotic growth medium which is specific to thegrowth of the Lactobacillus plantarum strain. The prebiotic growthmedium will preferably be capable of being producing by theLactobacillus plantarum strain by reverse enzyme reaction. The prebioticgrowth medium may comprise oligosaccharides, which will preferablycomprise galacto-oligosaccharide (GOS).

Preferably, the Lactobacillus plantarum is stored at 4° C. or belowbefore administration.

In accordance with yet a further aspect of the present invention, thereis provided a method of producing Lactobacillus plantarum 2830 (ECGC13110402), or mutant strain or strains thereof, for use in thepreparation of a medicament or food supplement, comprising:

-   -   a) fermenting Lactobacillus plantarum under conditions        sufficient to produce a culture broth;    -   b) concentrating the Lactobacillus plantarum from the culture        broth so as to form a concentrate of the Lactobacillus plantarum        cells;    -   c) subjecting the concentrate to a cryoprotectant so as to form        a mixture; and    -   d) freeze drying the mixture.

The survival rates for freeze drying the Lactobacillus plantarum cellsby such a method is over 70%. Furthermore, the method has beenadvantageously found that the method produces the Lactobacillusplantarum cells in amounts of up to 8×10¹¹ cfu/g.

The method will of course be suitable for producing Lactobacillusplantarum 2830 (ECGC 13110402), or mutant strain or strains thereof, fora composition as herein above described, or indeed the Lactobacillusplantarum 2830 (ECGC 13110402) as herein above described.

It will be apparent to the skilled addressee that a number of thefeatures of the composition listed in respect to the first aspect of theinvention will be interchangeable with the composition administered inthe present method.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention will now be described, by way ofexample only.

A human volunteer study was conducted to establish the safety,compliance and extent of hypertension control by administeringcompositions comprising Lactobacillus plantarum ECGC 13110402 to 49mildly hypercholesterolaemic adults. The study was carried outindependently by the Department of Food and Nutritional Sciences at theUniversity of Reading, UK. The study was carried out according to theHelsinki declaration and written informed consent was obtained from allvolunteers. The study protocol was approved by the Research Ethicscommittee of the University of Reading.

Subjects were male or female, aged 30-65 years. Subjects were excludedif they had had a previous cardiovascular event within the last 6months, if secondary dyslipemias related to thyroid dysfunction werepresent, if they had used any drug affecting lipid metabolism in theprevious 3 months, if they had a history of alcohol abuse, if they hadtaken antibiotics in the previous 6 months or if they had takenprebiotics/probiotic preparations in the last month.

Those who met the inclusion criteria were screened prior to thecommencement of the study. A baseline blood sample was taken and theirBMI and blood pressure were measured.

The study was a single-centre, prospective, randomized, double-blind,placebo-controlled, parallel-group trial. Subjects were randomlydistributed into two groups: placebo or treatment with Lactobacillusplantarum ECGC 13110402. The placebo and treatment groups were providedwith a blister packed DR 1 capsule. The treatment group received 120 mgof active Lactobacillus plantarum ECGC 13110402 providing a dose of1.8×10⁹ cells per capsule which was administered twice daily; once atbreakfast and once in the evening. Participants were advised not tochange their regular diet or physical activity throughout the trialperiod. Habitual diet was assessed by pre-validated 5-day food diaries(2 weekend and 3 week days).

Formulation details for the active and placebo formulations respectivelyare shown in tables 1 and 2 below:

TABLE 1 Billion g for Ingredient mg/capsule for capsule productionProbiotic powder 120 8.4 × 10⁹ 567.00 Corn starch 118.6 560.39 Magnesiumstearate 3.2 15.12 Silicon dioxide 3.2 15.12 Capsule DR size 1 white 75354.38 TOTAL 320 1512

TABLE 2 Billion g for Ingredient mg/capsule for capsule production Cornstarch 238.6 1127.39 Magnesium stearate 3.2 15.12 Silicon dioxide 3.215.12 Capsule DR size 1 white 75 354.38 TOTAL 320 1512

Volunteers were pre-screened 2 weeks prior to the study start and wereadvised to refrain from any pre/probiotic intake. The study consisted oftwo phases: a treatment period (12 weeks) and a wash-out period (4weeks). The study included a baseline visit at selection, a visit at themidpoint and at the endpoint of the treatment period (weeks 0, 6 and 12,respectively), and a fourth visit after the wash-out period (week 16).

An initial set of analyses examined the demographic and outcomevariables at baseline to ensure that the two groups were well matched.Continuous variables were analysed using the unpaired t-test, whilst theChi-square test was used for the categorical variables.

Study outcomes between the two study groups were analysed in terms ofchanges between timepoints. Four study periods were examined for changesin outcomes: baseline to midpoint (0-6 weeks), midpoint to endpoint(6-12 weeks), baseline to endpoint (0-12 weeks) and endpoint to washout(12-16 weeks). Data for each analysis was restricted to the particulartwo timepoints in the analysis. The analyses were performed usinganalysis of covariance (ANCOVA). The latter timepoint was used as theoutcome variable, with the earlier timepoint considered as a covariate.This approach is mathematically preferable to simply comparing thechange over time between groups, as it takes into account the variablestarting values for the test and control group.

There were no safety, compliance, or tolerance issues reported byvolunteers throughout the study. Three volunteers dropped out of thestudy due to antibiotic treatment for non related illnesses whichexcluded them from further study participation.

The baseline characteristics (anthropometric measurements, systolic anddiastolic pressure) were compared between the placebo (n=23) and active(n=23) groups and are shown in table 3 below. The results suggested nosignificant difference between the two study groups in terms of theirdemographics (age, sex) or for any of the anthropometric measures atbaseline.

TABLE 3 Placebo (n = 23) Active (n = 23) Variable Mean (SD) Mean (SD)P-value Age  52.0 (8.4)  52.3 (10.7) 0.89 Gender: Female   14 (61%)   18(78%) 0.20 Gender: Male   9 (39%)    5 (22%) Weight 79.2 (16.5)  72.1(12.0) 0.10 BMI  26.8 (5.0)  26.7 (3.7) 0.96 Waist 92.3 (13.5)  89.6(12.0) 0.49 Systolic BP 118.7 (16.0)  119.2 (13.2) 0.73 Diastolic BP71.0 (12.2)  73.0 (8.0) 0.52

Changes in anthropometric measurements for all subjects (n=46) in theplacebo and active treatment groups are shown from the baseline to theend of treatment after 12 weeks in table 4 below. The mean values andstandard deviation for each measured outcome at baseline and after 12weeks are shown in table 4. Group differences from the ANCOVA analysesare also shown with the mean difference and corresponding confidenceinterval. These are reported as outcome for active group minus outcomefor placebo group adjusting for the baseline value. P-values indicatingthe significance of the results are reported. Body weight is expressedin kg, BMI in kg/m², waist circumference in cm and systolic/diastolicpressure in mmHg.

TABLE 4 Group Change % Change Difference Baseline 12 weeks Mean (SD)Mean (SD) Mean P- Outcome Group Mean (SD) Mean (SD) [range] [range] (95%CI) value Weight Placebo 79.2 (16.5) 79.3 (16.8) 0.2 (1.7) 0.1 (2.1) 00.18 [−2.6, 3.5] [−3.3, 4.7] Active 72.1 (12.0) 72.8 (12.6) 0.7 (1.7)0.9 (2.2) 0.7 (−0.3, 1.7) [−2.6, 3.8] [−2.8, 4.9] BMI Placebo 26.8(5.0)  27.0 (5.2) 0.3 (1.3) 0.9 (4.7) 0 0.41 [−3.1, 4.2]  [−9.3, 15.5]Active 26.7 (3.7)  27.2 (4.0) 0.5 (0.9) 2.0 (3.3) 0.3 (−0.4, 1.0) [−1.1,3.3]  [−3.9, 11.8] Waist Placebo 92.3 (13.5) 90.5 (13.8) −1.8 (6.4) −1.8 (6.8)  0 0.61 [−14, 12] [−17.3, 12.9] Active 89.6 (12.0) 89.1(11.0) −0.5 (5.7)  −0.2 (6.7)  0.9 (−2.6, 4.4) [−13, 13]  [−13.0, 16.31Systolic Placebo 117.7 (16.0) 122.3 (11.4)  4.7 (11.0)  4.9 (10.3) 00.15 pressure [−13, 28] [−11.4, 31.1] Active 119.2 (13.2) 119.7 (13.0)0.5 (8.9) 0.7 (7.2) −3.6 (−8.6, 1.4)  118.45 [−19, 21] [−13.4, 15.8] −3%Diastolic Placebo 71.0 (12.2) 73.5 (8.2) 2.4 (9.0)  5.0 (13.6) 0 0.39pressure [−15, 18] [−14.4, 30.5] Active 73.0 (8.0)  73.0 (8.2) 0.0 (5.9)0.3 (8.4) −1.6 (−5.2, 2.1)  72   [−9, 13] [−10.5, 20.3] −2.2%  

No significant changes were noted in the anthropometric parametersrelevant to weight, BMI and waist circumference between baseline and endof treatment at 12 weeks.

There was group evidence of a difference in systolic and diastolic bloodpressure between baseline and 12 weeks. The difference in systolic bloodpressure was both statistically and clinically significant. In the allsubject active treatment group systolic blood pressure was 3.6 mmHglower (−3%) whilst diastolic pressure was reduced by 1.6 mmHg (2.2%).The majority of the reduction in systolic blood pressure occurred in the6-12 week time period. This showed a statistically significant reduction(P=0.003) in systolic blood pressure of 6 mmHg (5.1%) in the activegroup when compared to the placebo group (data not shown in table 4).This is higher than the mean 3 mmHg pulse pressure reduction achieved byACE inhibitors, ARBs and renin inhibitors and the 2 mmHg pulse pressurereduction with non-selective beta blockers. This reduction is alsogreater than the reduction of systolic BP by −3.56 mm Hg (95% confidenceinterval, −6.46 to −0.66) compared with control groups shown in a studyanalysing blood pressure reduction by probiotics (Khalesi et al, 2014).

The results show that Lactobacillus plantarum ECGC 13110402 has thepotential to lower systolic blood pressure in at least mildlyhypercholesterolaemic subjects.

Active Lactobacillus plantarum ECGC 13110402 and placebo capsules werestored at 4° C. throughout the study duration. Product stability waschecked at baseline, 6 weeks and 12 weeks (end of treatment) of thestudy and no significant change was observed in bacterial numbers. Nobacterial growth was detected in the placebo capsules.

Analysis of safety parameters did not show deleterious effects ofconsuming Lactobacillus plantarum (ECGC 13110402). Lactobacillusplantarum is a widely used probiotic which is considered GenerallyRegarded as Safe (GRAS) by the US Food and Drug Administration (FDA) andhas a Qualified Presumption of Safety (QPS) designation by the EuropeanFood Standard Agency. This would suggest that Lactobacillus plantarumECGC 13110402 has the potential to be a safe and effective treatment forthe treatment of hypertension.

Industrial scale-up experiments were also conducted on Lactobacillusplantarum ECGC 13110402. The following activities were performed: a)testing of flasks for different hypoallergenic media; b) fermentationsof 1-5 L, concentration and freeze drying of small amounts to study; c)testing of different cryoprotectants; d) testing of different freezedrying curves; e) fermentation in 80 L, concentration and freeze drying.The final step was a production in a 80 L fermenter which resulted in:(i) cell count >8×10¹¹ cfu/g; (ii) Aw: 0,11; (iii) a quantity of 700 gof concentrated biomass, freeze dried and not diluted/standardized withany excipient. Therefore, this particular strain looked extremelypromising from a manufacturing point of view. Survival rate of the cellswas found to be at more than 70% and yields were at 1.25% which isextremely high.

The forgoing embodiments are not intended to limit the scope of theprotection afforded by the claims, but rather to describe examples ofhow the invention may be put into practice.

BIOLOGICAL DEPOSITS

The application refers to the following indications of depositedbiological material:

-   -   Name: European Collection of Cell Cultures    -   Address: Public Health England Porton Down,        -   National Collection of Type Cultures,        -   PHE Culture Collections, Microbiological Services,        -   Porton Down,        -   Sailsbury,        -   SP4 0JG        -   United Kingdom

Date: 4 Nov. 2013

Accession Number: 13110402

1-44. (canceled)
 45. A composition comprising: Lactobacillus plantarum2830 deposited at the European Collection of Cell Cultures underAccession Number 13110402, or mutant strain or strains thereof, for usein the treatment or prevention of hypertension, wherein theLactobacillus plantarum 2830 is freeze-dried.
 46. The composition ofclaim 45, for use in the treatment or prevention of hypertension in anindividual having at least mild hypercholesterolaemia.
 47. Thecomposition of claim 45, wherein the composition is incorporated into afoodstuff, food supplement, or drinkable liquid.
 48. The composition ofclaim 45, wherein the Lactobacillus plantarum 2830 or the mutant strainor strains thereof is administered in a dose in the range of 10⁵ cfu/gto 10¹² cfu/g.
 49. The composition of claim 45, wherein the compositionis administered once or twice daily and/or wherein the composition isadministered or taken after or during meals.
 50. The composition ofclaim 45, wherein the Lactobacillus plantarum 2830 is furtherconcentrated.
 51. The composition of claim 45, wherein the compositionfurther comprises one or more active ingredients selected from:vitamins, minerals, phytochemicals, antioxidants, and combinationsthereof.
 52. The composition of claim 45, wherein the compositionfurther comprises one or more additional hypertension reducing agents.53. The composition of claim 45, wherein the composition is administeredor taken in combination with one or more of the following: statins,sterols and/or stanols.
 54. The composition of claim 45, wherein thecomposition is stored at 4° C. or below.
 55. The composition of claim45, further comprising a prebiotic growth medium which is specific tothe growth of the Lactobacillus plantarum 2830 or the mutant strain orstrains thereof, and wherein the prebiotic growth medium is capable ofbeing produced by the Lactobacillus plantarum 2830 or the mutant strainor strains thereof by reverse enzyme reaction.
 56. The composition ofclaim 55, wherein the prebiotic growth medium comprisesoligosaccharides.
 57. The composition of claim 56, wherein theoligosaccharides comprise galacto-oligosaccharide (GOS).
 58. A method oftreating an individual with, or at risk of, hypertension comprising:administering the composition according to claim
 1. 59. The method ofclaim 58, wherein the Lactobacillus plantarum 2830 or the mutant strainor strains thereof is administered in an amount in the range of 10⁵cfu/g to 10¹² cfu/g.
 60. The method of claim 58, wherein the compositionis administered twice daily and/or administered during or after meals.61. The method of claim 58, wherein the composition further comprisesone or more active ingredients selected from: vitamins, minerals,phytochemicals, antioxidants and combinations thereof.
 62. The method ofclaim 58, wherein the composition further comprises one or morecholesterol reducing agents.
 63. The method of claim 58, wherein thecomposition is administered in combination with one or more of thefollowing: statins, sterols and/or stanols.
 64. The method of claim 58,wherein the composition is stored at 4° C. or below.